{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:24:06Z","timestamp":1783427046178,"version":"3.54.6"},"reference-count":32,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"AstraZeneca"},{"DOI":"10.13039\/100019966","name":"Honeywell International Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019966","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>HFO-1234ze (E) is proposed as a near zero global warming propellant for use in metered dose inhaled (MDI) products. This paper describes the non-clinical safety assessment in mice, rats, and dogs and supplements previously reported data (genetic toxicology, short-term toxicology, and reproductive toxicology). In all species, HFO-1234ze (E) was only detectable in blood for a short period after dosing with no evidence of accumulation. HFO-1234ze (E) was without any toxicological effects at very high doses in subchronic (13-week mouse) and chronic (39-week dog) studies. Chronic (26-week) administration to rats at very high doses was associated with an exacerbation of rodent progressive cardiomyopathy, a well-documented background finding in rodents. In a 2-generation study, extremely high doses were associated with the early euthanasia of some lactating female rats. This finding was considered to be significantly influenced by a state of negative energy balance, reflecting the specific vulnerability of rats during lactation. These findings are considered to not pose a risk to humans with typical MDI use given they occurred at doses which far exceed those expected in patients. Overall, the nonclinical safety data for HFO-1234ze (E) support its further development as an MDI propellant.<\/jats:p>","DOI":"10.1177\/10915818231206025","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T05:29:54Z","timestamp":1697779794000},"page":"4-18","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["The Nonclinical Assessment of Trans-1,3,3,3-tetrafluoropropene (HFO-1234ze (E)), a Near Zero Global Warming Potential Propellant for Use in Metered Dose Inhalation Products"],"prefix":"10.1177","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-0127","authenticated-orcid":false,"given":"Paul S.","family":"Giffen","sequence":"first","affiliation":[{"name":"Department of Respiratory & Immunology Toxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne D.","family":"Kilgour","sequence":"additional","affiliation":[{"name":"ApconiX, Macclesfield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-1188","authenticated-orcid":false,"given":"Matthew","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Thacker","sequence":"additional","affiliation":[{"name":"Department of Regulatory Toxicology and Safety Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann A.","family":"Holmberg","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"issue":"9","key":"bibr1-10915818231206025","first-page":"1177","volume":"50","author":"Newman SP","year":"2005","journal-title":"Respir Care"},{"issue":"9","key":"bibr2-10915818231206025","first-page":"1201","volume":"50","author":"Leach CL","year":"2005","journal-title":"Respir Care"},{"key":"bibr3-10915818231206025","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S262141"},{"key":"bibr4-10915818231206025","unstructured":"European Union (EU) Regulation No 517\/2014 of the European Parliament and of the Council of 16 April 2014 on fluorinated greenhouse gases and repealing Regulation (EC) No 842\/2006. 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